PII-116 - EXPOSURE RESPONSE (E-R) RELATIONSHIPS OF LISOCABTAGENE MARALEUCEL (LISO-CEL) MONOTHERAPY IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL)

Y. Chen¹, N. Balasubramanian², J. Cummings², H. Lin², S. Ou³, S. Tuazon³, S. Perna³, K. Ogasawara²; ¹Clinical pharmacology and pharmacometrics, disposition and bioanalysis, ²Bristol Myers Squibb, ³BMS.

Background: Liso-cel has demonstrated durable and deep responses and a manageable safety profile in patients with heavily pretreated R/R CLL/SLL(N=117). Higher liso-cel expansion (maximum expansion (Cmax) and area under the curve from days 0-28 (AUC(0-28d)) were observed in responders (39/70, 56%) vs. in non-responders and in patients with undetectable minimum residual disease vs. those without. Here we further characterize the association between liso-cel expansion and selected clinical efficacy and safety endpoints from phase 1/2, single-arm, multicenter TRANSCEND CLL 004 study (NCT03331198).

Methods: Patients with R/R CLL/SLL previously treated with at least 2 prior lines of therapy, including a Bruton tyrosine kinase inhibitor were included. Patients received a single infusion of liso-cel at a dose of either 50 (DL1) or 100 (DL2) × 10^6 chimeric antigen receptor positive T cells Transgene levels in blood were monitored by quantitative polymerase chain reaction and the cellular kinetic (CK) parameters were calculated using noncompartmental analysis. E-R relationship of efficacy (DL2, N=70) and safety (DL1+2, N=97) was assessed by Wilcoxon test or Cox proportional hazards model

Results: Robust expansion of liso-cel across dose levels were observed with a median time to Cmax of 14 days and persistence up to 36 months after infusion in 1 of 4 evaluable patients. A potential association was observed between higher transgene CK parameters with achievement of CR by iwCLL 2018 (2.7-fold in Cmax & 2.3-fold in AUC(0-28d), p < 0.05) and longer progression free survival (PFS) [hazard ratio (95% Confidence Interval): 0.30 (0.19, 0.48) for Cmax & 0.36 (0.23, 0.55) for AUC(0-28d), p < 0.05]. No apparent association was observed between transgene CK parameters and duration of response or complete response. Higher transgene CK parameters was associated with the occurrence of any grade cytokine release syndrome (CRS) (38-fold in Cmax and 44-fold in AUC(0-28d), p < 0.05), grade ≥ 3 CRS (4.7-fold in Cmax & 6.1-fold in AUC(0-28d), p < 0.05), any grade neurological event (NE), and grade ≥ 3 NE (approx. 2- fold in Cmax & AUC(0-28d) in both cases, p < 0.05)

Conclusion: Higher liso-cel expansion is associated with achieving CR, longer PFS, and the occurrence of any grade or grade ≥ 3 CRS and NE in patients with R/R CLL/SLL